Non-aqueous patch

ABSTRACT

Non-aqueous patches comprising lidocaine, which is not dissolved and is present in a crystalline state, have poor permeability to the skin. Therefore, non-aqueous patches have a high concentration of lidocaine. It is pointed out that lidocaine has an adverse effect on the heart. Prolonged use of a high concentration of lidocaine causes side effects, such as shock, rubor, and irritating sensation. External preparations comprising more than 5 mass % of lidocaine are designated as powerful drugs, and cannot be used as household (nonprescription) medicine. Provided is a non-aqueous patch that is effective to relieve muscle pain, the non-aqueous patch comprising lidocaine and/or its reactant, and a dissolving agent composed of an organic acid and a polyalcohol, which are contained in a base.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/065,075, filed on Mar. 9, 2016, which is a divisional of Ser. No.14/116,730, filed on Feb. 3, 2014, now U.S. Pat. No. 9,283,174, issuedon Mar. 15, 2016 which is a 35 U.S.C. § 371 national stage filing ofInternational Application No. PCT/JP2011/060781, filed on May 10, 2011.The entire contents of these applications are explicitly incorporatedherein by reference.

TECHNICAL FIELD

The present invention relates to a non-aqueous patch for medical andhome use using lidocaine.

BACKGROUND ART

Lidocaine is used for the purpose of local anesthesia or topicalanesthesia. The usage form of lidocaine is an external preparationcomprising lidocaine or a patch comprising lidocaine. Examples ofexternal preparations include ointment, cream, jelly, spray, etc., whichare used, for example, for topical anesthesia of the skin in thetreatment of postherpetic neuralgia. Examples of patches include aqueousbase patches (cataplasms) and non-aqueous patches (tapes).

An example of aqueous base patches is Lidoderm (registered trademark ofEndo Pharmaceuticals (U.S.)), which is mainly used for topicalanesthesia of the skin in the treatment of postherpetic neuralgia, andis also used to relieve pain in various muscles. Aqueous base patcheshave thick plasters because they contain moisture; therefore, aqueousbase patches are poorly compatible with the skin. Moreover, due to verylittle adhesion, aqueous base patches are difficult to be attached tothe skin for a long period of time. Furthermore, the vaporization ofmoisture problematically causes changes in adhesion and physicalproperties. Additionally, in order to make lidocaine permeate into themuscle, it is necessary to dissolve lidocaine, and moisture is thusrequired to dissolve lidocaine.

Next, as a non-aqueous patch, for example, Patent Japanese Patent No.3159688 (patent Document 1) discloses a technique for alleviatingpostherpetic neuralgia, in which 5 to 30 wt. % of lidocaine is added asa local anesthetic. Japanese Unexamined Patent Publication No. 7-215850(Patent Document 2) discloses a technique relating to a percutaneousabsorption tape for local anesthesia comprising 5 to 100 wt. % oflidocaine. Japanese Unexamined Patent Publication No. 9-315964 (PatentDocument 3) and Japanese Unexamined Patent Publication No. 2001-392501(Patent Document 4) disclose techniques relating to a patch comprising0.5 to 5 mass % of lidocaine. WO 2009/060629 (Patent Document 5)discloses a technique relating to a patch comprising 10 to 40 mass % oflidocaine. These non-aqueous patches have poor permeability to the skinbecause the lidocaine is not dissolved and is present in a crystallinestate.

In addition, the technique disclosed in Patent Document 5 uses a highconcentration of lidocaine. It is pointed out that lidocaine has anadverse effect on the heart. Prolonged use of a high concentration oflidocaine causes side effects, such as shock, rubor, and irritatingsensation. External preparations comprising more than 5 mass % oflidocaine are designated as powerful drugs, and cannot be used ashousehold (nonprescription) medicine.

In contrast, the techniques disclosed in Patent Documents 3 and 4 use asmall amount of lidocaine, and can be used for household use; however,even after the small amount of lidocaine is completely dissolved, thelidocaine cannot be stably released over a long period of time (e.g., 12hours or more) and cannot permeate into the skin. Thus, there is aproblem with the pain-relieving effect.

SUMMARY OF INVENTION Technical Problem

Using lidocaine, which has the effect of relieving pain in the skin whena needle is punctured, the present inventors focused on the developmentof a non-aqueous patch for relieving muscular pain through the skin.

For this purpose, the present inventors first focused on the use of asmall amount of lidocaine, not a high concentration of lidocaine, in theplaster, and on the complete dissolution of lidocaine so that the smallamount of lidocaine is percutaneously absorbed stably over a long periodof time and permeates into the muscle. When these requirements aresatisfied, lidocaine can be used as a non-aqueous patch that can relievemuscular pain over a long period of time.

Solution to Problem

Accordingly, in the present invention, a dissolving agent composed of anorganic acid and a polyalcohol was used, and 0.5 to 7 mass % oflidocaine and/or its reactant was mixed in a plaster, thereby producinga non-aqueous patch in which the lidocaine is completely dissolved, andwhich is effective to relieve various muscle pains over a long period oftime. The amount of lidocaine and/or its reactant in the plaster ispreferably 0.1 to 1 mg/cm².

The non-aqueous patch is required to have a low plaster mass. When thesize of one patch is 14×10 cm, the plaster mass is 0.84 to 2.8 g.Because the lidocaine content of the plaster is 0.5 to 7 mass %, theamount of lidocaine per patch can be kept as 196 mg or less.

In order to make lidocaine present uniformly and stably in the plasterfor effective use, the lidocaine content is set to be 0.5 to 7 mass %.The reason for this is that when the lidocaine content is less than 0.5mass %, the effect of relieving various muscle pains is low, and thedesired effectiveness cannot be achieved. In contrast, when thelidocaine content is more than 7 mass %, a large amount of dissolvingagent is required to ensure the release of lidocaine. The adhesion ofthe patch is thereby reduced, and the physical properties of the patchcannot be maintained, failing to cause the patch to be sufficientlyattached to the affected part. Another reason is that the lidocainecontent is desired to be low.

According to the present invention, a small amount of lidocaine isefficiently dissolved, and thereby the lidocaine can be released stablyand reliably over a long period of time.

Particularly, the present invention is focused on a dissolving agentthat can efficiently dissolve lidocaine over a long period of time,revealing that a dissolving agent composed of a mixture of an organicacid and a polyalcohol allows continuous and reliable dissolution oflidocaine.

Examples of organic acids include acetic acid, oleic acid, isostearicacid, etc.

Examples of polyalcohols include 1,3-butylene glycol, propylene glycol,dipropylene glycol, polyethylene glycol, glycerin, etc.

The most effective proportion of dissolving agent and lidocaine is 0.5to 5 mass % of dissolving agent relative to 1 mass % of lidocaine. Inthis proportion, lidocaine can be stably mixed in a dissolved state,increasing the release rate of the lidocaine to the skin, and causingthe drug to effectively permeate into the muscle. Here, the reason forthis proportion, i.e., 0.5 to 5 mass % of dissolving agent relative to 1mass % of lidocaine, is as follows. When the amount of dissolving agentis less than 0.5 mass %, lidocaine cannot be stably dissolved and cannottherefore be favorably released. In contrast, when the amount ofdissolving agent is more than 5 mass %, the adhesion of the patchdecreases, and sufficient attaching power to the skin cannot beachieved.

Although general starting materials for non-aqueous patches can be usedfor the plaster, the patch can maintain moderate flexibility by using anelastomer as the base. As the elastomer usable as the base, for example,isoprene rubber, polyisobutylene, and styrene isoprene rubber arepreferably used. The amount of elastomer is preferably 10 to 50 mass %,and more preferably 20 to 40 mass %, based on 100 mass % of the plaster.

Further, a tackifier resin for increasing adhesive power can be freelyadded. Usable examples thereof include rosin-based resin, syntheticpetroleum resin, terpene resin, phenol resin, alicyclic petroleum resin,and other resins that are generally used in patches. Polybutene orliquid paraffin may be added as a softener, and menthol, camphor, or thelike may be added as a skin stimulant. Moreover, anhydrous silicic acid,zinc oxide, or other inorganic substances, zinc stearate,polyvinylpyrrolidone, or the like can be used as a regulator.Furthermore, antioxidants, UV absorbers, preservatives, sequestrants,and other additives that are designed to prevent the degradation ofpreparations may be used.

The plaster prepared by mixing these starting materials is held by asubstrate comprising nonwoven fabric, woven fabric, knitted fabric,film, or a combination thereof, which can be generally used for patches.As a peeling film covering the plaster surface, a film moderatelysubjected to a mold release treatment is generally used. Since the drugmay be adsorbed to the substrate or peeling film, polyester is generallyused as their material; however, any materials can be used unless theycause problems.

The mass of the plaster is preferably in the range of 60 to 200 g/m²,and more preferably 80 to 180 g/m². When the plaster mass is less than60 g/m², it is necessary to increase the proportion of lidocaine to theentire plaster, in order to maintain the sufficient efficacy oflidocaine. In this case, however, lidocaine is not sufficientlydissolved and is crystallized; the crystallized lidocaine cannot beefficiently transferred to the skin. Additionally, it is difficult tocontrol the adhesion of the patch, and the plaster is not flexibleagainst the skin and fails to maintain moderate adhesion. In contrast,when the plaster mass is more than 200 g/m², the plaster is so heavythat plaster dripping easily occurs.

The method of producing the non-aqueous patch of the present inventionmay be a general method that is conventionally used, such as a hot meltmethod or a solvent method.

Advantageous Effects of Invention

The non-aqueous patch of the present invention allows the lidocaine inthe plaster to ensure a release rate of 10% or more after the patch isattached to the skin for 12 hours. Moreover, the non-aqueous patch witha low lidocaine content does not lead to abnormal skin penetration orrapid increase in blood levels after a long period of attachment or inthe damaged skin, etc., and results in fewer side effects. Thus, thenon-aqueous patch has efficiency and safety as a patch for use inrelieving various muscle pains.

Furthermore, in spite of a low lidocaine content, the non-aqueous patchcan be used for topical anesthesia of the skin, because the lidocainehas good solubility.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a graph showing the ratio of the remaining drug.

FIG. 2 is a graph showing blood levels.

FIG. 3 is a chart of formulations.

FIG. 4 is a chart of ball tack scores.

DESCRIPTION OF EMBODIMENTS

Examples of the present invention are described with reference to Table1.

Example 1

Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced byKraton JSR Elastomers K.K.): 18 mass % Polyisobutylene (trade name“Himol 6H”, produced by JX Nippon Oil & Energy Corporation): 5 mass %

Hydrogenated rosin ester (trade name “Pinecrystal KE-311”, produced byArakawa Chemical Industries, Ltd.): 12 mass %

Terpene resin (trade name “YS resin 1150N”, produced by YasuharaChemical Co., Ltd.): 10 mass %

Lidocaine: 7 mass %

1,3-butylene glycol (produced by Daicel Chemical Industries, Ltd.): 1.5mass %

Oleic acid (“Purified Oleic Acid”, produced by NOF Corporation): 2 mass%

Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation):43.8 mass %

Light anhydrous silicic acid (trade name “Sylysia 350”, produced by FujiSilysia Chemical Ltd.): 0.5 mass %

Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu ChemicalIndustry Co., Ltd.): 0.2 mass %

The production method using these materials according to the aboveformulation was as follows. The styrene-isoprene-styrene blockcopolymer, polyisobutylene, hydrogenated rosin ester, terpene resin,light anhydrous silicic acid, dibutylhydroxytoluene, and liquid paraffinwere placed in a dissolution mixer and dissolved under heating at 150°C. A solution separately prepared by mixing the lidocaine, 1,3-butyleneglycol, and oleic acid, followed by dissolution at 80° C., was addedthereto, and the mixture was mixed under heating at 140° C. until themixture became homogeneous, thereby obtaining a plaster solution. Theplaster solution was applied to a polyester film treated with silicon sothat the plaster weight was 140 g/m². A polyester woven fabric waspasted thereto and cooled. The resultant was then cut into a rectangle(about 14 cm×10 cm). In this preparation, the proportion of lidocaineand dissolving agent was 1:0.5 by mass ratio.

Example 2

Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced byKraton JSR Elastomers K.K.): 15 mass %

Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil &Energy Corporation): 10 mass %

Terpene resin (trade name “YS resin 1150N”, produced by YasuharaChemical Co., Ltd.): 20 mass %

Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation):48.3 mass %

Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.5 mass %

Lidocaine: 3 mass %

1,3-butylene glycol (produced by Daicel Chemical Industries, Ltd.): 1.5mass %

Light anhydrous silicic acid (trade name “Sylysia 350”, produced by FujiSilysia Chemical Ltd.): 0.5 mass %

Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu ChemicalIndustry Co., Ltd.): 0.2 mass %

The production method using these materials according to the aboveformulation was as follows. The styrene-isoprene-styrene blockcopolymer, polyisobutylene, terpene resin, light anhydrous silicic acid,dibutylhydroxytoluene, and liquid paraffin were placed in a dissolutionmixer and dissolved under heating at 150° C. A solution separatelyprepared by mixing the isostearic acid, lidocaine, and 1,3-butyleneglycol, followed by dissolution at 80° C., was added thereto, and themixture was mixed under heating at 140° C. until the mixture becamehomogeneous, thereby obtaining a plaster solution. The plaster solutionwas applied to a polyester film treated with silicon so that the plasterweight was 140 g/m². A polyester woven fabric was pasted thereto andcooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).In this preparation, the proportion of lidocaine and dissolving agentwas 1:1 by mass ratio.

Example 3

Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced byKraton JSR Elastomers K.K.): 18 mass %

Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil &Energy Corporation): 10 mass %

Terpene resin (trade name “YS resin 1150N”, produced by YasuharaChemical Co., Ltd.): 20 mass %

Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation):46.9 mass %

Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.8 mass %

Dipropylene glycol (produced by NOF Corporation): 0.5 mass %

Lidocaine: 2 mass %

Light anhydrous silicic acid (trade name “Sylysia 350”, produced by FujiSilysia Chemical Ltd.): 0.5 mass %

Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu ChemicalIndustry Co., Ltd.): 0.3 mass %

The production method using these materials according to the aboveformulation was as follows. The styrene-isoprene-styrene blockcopolymer, polyisobutylene, terpene resin, light anhydrous silicic acid,dibutylhydroxytoluene, and liquid paraffin were placed in a dissolutionmixer and dissolved under heating at 150° C. A solution separatelyprepared by mixing the isostearic acid, lidocaine, and dipropyleneglycol, followed by dissolution at 80° C., was added thereto, and themixture was mixed under heating at 140° C. until the mixture becamehomogeneous, thereby obtaining a plaster solution. The plaster solutionwas applied to a polyester film treated with silicon so that the plasterweight was 140 g/m². A polyester nonwoven fabric was pasted thereto andcooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).In this preparation, the proportion of lidocaine and dissolving agentwas 1:1.15 by mass ratio.

Example 4

Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced byKraton JSR Elastomers K.K.): 20 mass %

Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil &Energy Corporation): 8 mass %

Hydrogenated rosin ester (trade name “Pinecrystal KE-311”, produced byArakawa Chemical Industries, Ltd.): 20 mass %

Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation):48.2 mass %

Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.5 mass %

Lidocaine: 0.5 mass %

1,3-butylene glycol (produced by Daicel Chemical Industries, Ltd.): 1mass %

Light anhydrous silicic acid (trade name “Sylysia 350”, produced by FujiSilysia Chemical Ltd.): 0.5 mass %

Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu ChemicalIndustry Co., Ltd.): 0.3 mass %

The production method using these materials according to the aboveformulation was as follows. The styrene-isoprene-styrene blockcopolymer, polyisobutylene, hydrogenated rosin ester, light anhydroussilicic acid, dibutylhydroxytoluene, and liquid paraffin were placed ina dissolution mixer and dissolved under heating at 150° C. A solutionseparately prepared by mixing the isostearic acid, lidocaine, and1,3-butylene glycol, followed by dissolution at 80° C., was addedthereto, and the mixture was mixed under heating at 140° C. until themixture became homogeneous, thereby obtaining a plaster solution. Theplaster solution was applied to a polyester film treated with silicon sothat the plaster weight was 160 g/m². A polyester nonwoven fabric waspasted thereto and cooled. The resultant was then cut into a rectangle(about 14 cm×10 cm). In this preparation, the proportion of lidocaineand dissolving agent was 1:5 by mass ratio.

Example 5

Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced byKraton JSR Elastomers K.K.): 18 mass %

Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil &Energy Corporation): 5 mass %

Hydrogenated rosin ester (trade name “Pinecrystal KE-311”, produced byArakawa Chemical Industries, Ltd.): 12 mass %

Terpene resin (trade name “YS resin 1150N”, produced by YasuharaChemical Co., Ltd.): 10 mass %

Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation):38.1 mass %

Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 2.1 mass %

Lidocaine: 7 mass %

Dipropylene glycol (produced by NOF Corporation): 7 mass %

Light anhydrous silicic acid (trade name “Sylysia 350”, produced by FujiSilysia Chemical Ltd.): 0.5 mass %

Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu ChemicalIndustry Co., Ltd.): 0.3 mass %

The production method using these materials according to the aboveformulation was as follows. The styrene-isoprene-styrene blockcopolymer, polyisobutylene, hydrogenated rosin ester, light anhydroussilicic acid, dibutylhydroxytoluene, and liquid paraffin were placed ina dissolution mixer and dissolved under heating at 150° C. A solutionseparately prepared by mixing the isostearic acid, lidocaine, anddipropylene glycol, followed by dissolution at 80° C., was addedthereto, and the mixture was mixed under heating at 140° C. until themixture became homogeneous, thereby obtaining a plaster solution. Theplaster solution was applied to a polyester film treated with silicon sothat the plaster weight was 100 g/m². A polyester nonwoven fabric waspasted thereto and cooled. The resultant was then cut into a rectangle(about 14 cm×10 cm). In this preparation, the proportion of lidocaineand dissolving agent was 1:1.3 by mass ratio.

Example 6

Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced byKraton JSR Elastomers K.K.): 20 mass %

Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil &Energy Corporation): 8 mass %

Terpene resin (trade name “YS resin 1150N”, produced by YasuharaChemical Co., Ltd.): 20 mass %

Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation):49.165 mass %

Isostearic acid (produced by Kokyu Alcohol Kogyo Co., Ltd.): 1.4 mass %

Lidocaine: 0.7 mass %

Dipropylene glycol (produced by NOF Corporation): 0.035 mass %

Light anhydrous silicic acid (trade name “Sylysia 350”, produced by FujiSilysia Chemical Ltd.): 0.5 mass %

Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu ChemicalIndustry Co., Ltd.): 0.2 mass %

The production method using these materials according to the aboveformulation was as follows. The styrene-isoprene-styrene blockcopolymer, polyisobutylene, terpene resin, light anhydrous silicic acid,dibutylhydroxytoluene, and liquid paraffin were placed in a dissolutionmixer and dissolved under heating at 150° C. A solution separatelyprepared by mixing the isostearic acid, lidocaine, and dipropyleneglycol, followed by dissolution at 80° C., was added thereto, and themixture was mixed under heating at 140° C. until the mixture becamehomogeneous, thereby obtaining a plaster solution. The plaster solutionwas applied to a polyester film treated with silicon so that the plasterweight was 150 g/m². A polyester nonwoven fabric was pasted thereto andcooled. The resultant was then cut into a rectangle (about 14 cm×10 cm).In this preparation, the proportion of lidocaine and dissolving agentwas 1:2.05 by mass ratio.

Comparative Example 1

Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced byKraton JSR Elastomers K.K.): 20 mass %

Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil &Energy Corporation): 5 mass %

Hydrogenated rosin ester (trade name “Pinecrystal KE-311”, produced byArakawa Chemical Industries, Ltd.): 15 mass %

Terpene resin (trade name “YS resin 1150N”, produced by YasuharaChemical Co., Ltd.): 5 mass %

Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation):48.2 mass %

Polysorbate 80 (produced by NOF Corporation): 4 mass %

Lidocaine: 2 mass %

Light anhydrous silicic acid (trade name “Sylysia 350”, produced by FujiSilysia Chemical Ltd.): 0.5 mass %

Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu ChemicalIndustry Co., Ltd.): 0.3 mass %

The production method using these materials according to the aboveformulation was as follows. The styrene-isoprene-styrene blockcopolymer, polyisoprene, hydrogenated rosin ester, terpene resin, lightanhydrous silicic acid, dibutylhydroxytoluene, and liquid paraffin wereplaced in a dissolution mixer and dissolved under heating at 150° C. Asolution separately prepared by mixing the Polysorbate 80 and lidocaine,followed by dissolution at 80° C., was added thereto, and the mixturewas mixed under heating at 140° C. until the mixture became homogeneous,thereby obtaining a plaster solution. The plaster solution was appliedto a polyester film treated with silicon so that the plaster weight was140 g/m². A polyester nonwoven fabric was pasted thereto and cooled. Theresultant was then cut into a rectangle (about 14 cm×10 cm).

Comparative Example 2

Styrene-isoprene-styrene block copolymer (“Kraton D1161”, produced byKraton JSR Elastomers K.K.): 15 mass %

Polyisobutylene (trade name “Himol 6H”, produced by JX Nippon Oil &Energy Corporation): 10 mass %

Terpene resin (trade name “YS resin 1150N”, produced by YasuharaChemical Co., Ltd.): 20 mass %

Liquid paraffin (trade name “Hicall”, produced by Kaneda Corporation):51.3 mass %

Lidocaine: 3 mass %

Light anhydrous silicic acid (trade name “Sylysia 350”, produced by FujiSilysia Chemical Ltd.): 0.5 mass %

Dibutylhydroxytoluene (trade name “BHT”, produced by Honshu ChemicalIndustry Co., Ltd.): 0.2 mass %

The production method using these materials according to the aboveformulation was as follows. The styrene-isoprene-styrene blockcopolymer, polyisobutylene, terpene resin, light anhydrous silicic acid,dibutylhydroxytoluene, and liquid paraffin were placed in a dissolutionmixer and dissolved under heating at 150° C. The lidocaine was addedthereto, and the mixture was mixed under heating at 140° C. until themixture became homogeneous, thereby obtaining a plaster solution. Theplaster solution was applied to a polyester film treated with silicon sothat the plaster weight was 140 g/m². A polyester nonwoven fabric waspasted thereto and cooled. The resultant was then cut into a rectangle(about 14 cm×10 cm).

[Table 1]

The preparations obtained in Examples 1 to 6 and Comparative Examples 1and 2 were subjected to the following tests.

Adhesion Test

A ball tack adhesion test was performed according to the test methoddescribed in Drug Approval and Licensing Procedures in Japan. As shownin Table 2, Examples 1 to 6 (hereinafter referred to the “inventionproducts”) showed excellent adhesion. The adhesion of ComparativeExample 1 was about half of those of the invention products. ComparativeExample 2 had satisfactory adhesion, because no dissolving agent wasused.

[Table 2]

Drug Remaining Test

As shown in FIG. 1, the preparations were attached to the human skin for4 hours, 8 hours, and 12 hours. After each time period was passed, thepreparations were removed. The amount of drug remaining in eachpreparation was measured to determine the drug remaining ratio on thepremise that the amount of drug prior to attachment was 100%.

The drug remaining ratio after attachment for 12 hours was 96 to 99% inthe comparative examples, while the results of all of the inventionproducts were 80% or less, and the amount of drug released into thehuman skin was 20% or more.

Blood Level Test

The preparations were attached to the human skin for 12 hours and thenremoved. 4 hours, 8 hours, and 12 hours after the attachment of thepreparations, and 24 hours after the removal of the preparations, theblood was extracted, and the level of lidocaine in the blood wasmeasured. FIG. 2 is a graph showing the results.

The results reveal that the preparations comprising a dissolving agentcomposed of isostearic acid and dipropylene glycol showed generally goodresults.

The invention claimed is:
 1. A non-aqueous patch comprising 0.5 to 7mass % lidocaine, and a dissolving agent consisting essentially of anorganic acid and a polyalcohol, which are contained in a plaster,wherein the amount of lidocaine is 0.1 to 1 mg/cm2 of the plaster, andwherein the proportion of dissolving agent to lidocaine is 0.5 to 5 mass% of dissolving agent relative to 1 mass % of lidocaine.
 2. Thenon-aqueous patch according to claim 1, wherein the organic acid isisostearic acid.
 3. The non-aqueous patch according to claim 1, whereinthe polyalcohol is dipropylene glycol.
 4. The non-aqueous patchaccording to claim 1, wherein the dissolving agent consists essentiallyof isostearic acid and dipropylene glycol.
 5. The non-aqueous patchaccording to claim 1 wherein the plaster is adhered to a polyester wovenfabric.
 6. The non-aqueous patch according to claim 1 wherein thelidocaine is completely dissolved in the dissolving agent.
 7. Thenon-aqueous patch of claim 1, wherein the mass of the plaster is fromabout 60 to 200 g/m2.
 8. The non-aqueous patch of claim 7 wherein themass of the plaster is from 80 to 180 g/m2.
 9. The non-aqueous patchaccording to claim 1 wherein the lidocaine is completely dissolved inthe plaster.
 10. The non-aqueous patch according to claim 1 furthercomprising an elastomer.
 11. The non-aqueous patch according to claim10, wherein the elastomer consists of polyisobutylene and styreneisoprene rubber.
 12. The non-aqueous patch according to claim 11 furthercomprising a tackifier resin selected from the group consisting ofterpene resin, rosin-based resin, alicyclic petroleum resin, phenolicresin and combinations thereof.
 13. The non-aqueous patch according toclaim 12, further comprising liquid paraffin.
 14. The non-aqueous patchaccording to claim 1, wherein the plaster is held by a substrateselected from the group consisting of nonwoven fabric, woven fabric,knitted fabric or a combination thereof.
 15. The non-aqueous patchaccording to claim 1, wherein the amount of lidocaine is 196 mg or less.